Description

Strain Information

Former Names C57BL/6-Shank3tm1.1Bux/J    (Changed: 02-MAY-12 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   13-MAR-13 Species laboratory mouse Generation ?pN1+F1 (14-MAR-13) Generation Definitions   Donating Investigator Joseph D Buxbaum,   Mount Sinai School of Medicine

Description
The Shank3^{flox ex4-9} allele has loxP sites flanking exons 4-9 of the SH3/ankyrin domain gene 3 gene (Shank3). When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding the ankyrin repeat domains deleted in the cre-expressing tissues. As SHANK3 is necessary for forming functional glutamatergic synapses between receptors and cytoskeletal/scaffolding elements, these floxed mice may be used to generate tissue-specific Shank3 deletions for studying synaptic glutamate receptor development/function, transmission and plasticity, as well as Shank3 haploinsufficiency, neurobehavioral manifestations of 22q13 deletion syndrome and/or autism spectrum disorders.

Development
A targeting vector was designed to insert a loxP site upstream of exon 4, and an frt-flanked PGK-neo cassette followed by a second loxP site all downstream of exon 9 of the targeted gene. The construct was electroporated into B6.Cg-Thy1^a-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric males were bred with C57BL/6NTac females to establish the colony. Next, mutant mice were bred with FLP-expressing mice (undisclosed genetic background) to remove the frt-flanked PGK-neo cassette. The resulting Shank3^{flox ex4-9} mice were then bred to C57BL/6NTac for two-to-three generations (and the FLP gene was removed) prior to sending to The Jackson Laboratory Repository (see SNP note below). Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish The Jackson Laboratory Repository colony. Of note, while backcrossing the donating investigator did not assay their colony at the Thy1 locus. As such, these mice may be segregating for the NZB-derived Thy1^a allele (from Bruce4 ES cells) or the C57BL/6-derived Thy1^b allele.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6J genetic background.

Control Information

	Control
	000664 C57BL/6J	(approximate)
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Shank3

017890	B6(Cg)-Shank3tm1.2Bux/J
017688	B6.129-Shank3tm2Gfng/J
017442	B6.129S7-Shank3tm1Yhj/J
018398	STOCK Shank3tm1.1Pfw/J

View Strains carrying other alleles of Shank3     (4 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Chromosome 22q13.3 Deletion Syndrome   (SHANK3) Schizophrenia 15; SCZD15   (SHANK3)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Shank3^tm1.1Bux/Shank3⁺

        involves: C57BL/6

• no phenotypic analysis
• *normal* no phenotypic analysis
  • only used to generate recombined allele   (MGI Ref ID J:175320)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cell Biology Research
Channel and Transporter Defects

Neurobiology Research
Behavioral and Learning Defects
Channel and Transporter Defects
      calcium: glutamate receptor
Cre-lox System
      loxP-flanked Sequences
Neurodevelopmental Defects
      Autism
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
      glutamate receptor: NMDA

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
      Tissue/Cell Markers: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Shank3tm1.1Bux
Allele Name		targeted mutation 1.1, Joseph D Buxbaum
Allele Type		Targeted (Floxed/Frt)
Mutation Made By		Joseph Buxbaum,   Mount Sinai School of Medicine
Strain of Origin		B6.Cg-Thy1
Gene Symbol and Name		Shank3, SH3/ankyrin domain gene 3
Chromosome		15
Gene Common Name(s)		AI841104; ProSAP2; expressed sequence AI841104;
Molecular Note		A loxP site was inserted upstream of exon 4 and an FRT flanked neo cassette and second loxP site were inserted downstream of exon 9 via homologous recombination. Flp mediated recombination removed the neo cassette. [MGI Ref ID J:175320]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Cre Melt Curve Analysis, Melt Curve Analysis
Shank3^tm1.1Bux, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bozdagi O; Sakurai T; Papapetrou D; Wang X; Dickstein DL; Takahashi N; Kajiwara Y; Yang M; Katz AM; Scattoni ML; Harris MJ; Saxena R; Silverman JL; Crawley JN; Zhou Q; Hof PR; Buxbaum JD. 2010. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 1(1):15. [PubMed: 21167025]  [MGI Ref ID J:175320]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   13-MAR-13

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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